Visna virus, a non-oncogenic retrovirus, is the etiologic agent of a slow demyelinating disease of sheep. The virus causes a lifelong persistent infection in the animal. Infected sheep develop vigorous immune responses which fail to cure the infection. The presence of virus specific DNA in the tissue of infected animals provides a mechanism for viral persistence, but it does not explain the continued expression of infectious virus as well as chronic progressive disease in the presence of neutralizing antibody. Studies in our laboratory have shown that progressive antigenic drift occurs in immune animals. Molecular analysis of these antigenic variants indicate that there is progressive accumulation of point mutations in the viral genome which probably codes for the viral glycoprotein. To understand the molecular events which result in antigenic variation and the molecular basis for viral neutralization we plan to continue our experiments genetically mapping and sequencing the evelope genes of visna virus and the closely related virus CAEV. Using the cloned viral DNAs from visna virus and an antigenic variant LV11 we plan to make recombinants to determine the genetic sites important in antigenic variation. Using the same approach, visna virus and CAEV recombinants will be used to determine what genetic factors determine whether neutralizing antibody is produced to the viral glycoprotein. Finally, monoclonal antibodies are being developed in our lab to investigate the structure of the envelope glycoprotein and to study the genetic sites of antigenic variation.